Evaluation of CRS3123 vs. Oral Vancomycin in Adult Patients With Clostridioides Difficile Infection

NCT ID: NCT04781387

Last Updated: 2025-06-13

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

43 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-05

Study Completion Date

2024-04-16

Brief Summary

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The purpose of this research is to evaluate the primary objectives of safety and efficacy (rate of clinical cure) of 2 dosages of CRS3123 (200 mg and 400 mg) administered orally (po) twice daily (bid) and vancomycin administered 125 mg PO 4 times daily (qid) in adults \> or equal to 18 years of age with a primary episode or first recurrence of CDI. The study will investigate the plasma concentrations and HRQoL outcomes of CRS3123 and additional efficacy endpoints as secondary objectives.

Detailed Description

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Conditions

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Clostridioides Difficile Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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CRS3123 200 milligram

CRS3123 200 milligram dose (400 mg/day) given orally at approximately 6-hour intervals for 10 days.

Due to the difference in dosing schedules between CRS3123 (twice a day) and the standard of care vancomycin (four times a day) and appearance of study drugs used in the 3 Arms, placebo will be used to match the total number of capsules in each arm.

Group Type EXPERIMENTAL

CRS3123

Intervention Type DRUG

Study drug dosed PO BID for a total of 10 days

CRS3123 400 milligram

CRS3123 400 milligram dose (800 mg/day) given orally at approximately 6-hour intervals for 10 days.

Due to the difference in dosing schedules between CRS3123 (twice a day) and the standard of care vancomycin (four times a day) and appearance of study drugs used in the 3 Arms, placebo will be used to match the total number of capsules in each arm.

Group Type EXPERIMENTAL

CRS3123

Intervention Type DRUG

Study drug dosed PO BID for a total of 10 days

Vancomycin 125 milligram

Vancomycin 125 milligram dose (500 mg/day) given orally at approximately 6-hour intervals for 10 days.

Group Type ACTIVE_COMPARATOR

Active Comparator

Intervention Type DRUG

Active comparator dosed PO QID for 10 days

Interventions

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CRS3123

Study drug dosed PO BID for a total of 10 days

Intervention Type DRUG

Active Comparator

Active comparator dosed PO QID for 10 days

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Adults, ≥ 18 years of age.
2. More than or equal to 3 diarrheal (Bristol Stool Scale scores 5, 6, or 7) stools/day in a 24-hour period during screening prior to randomization and in the judgment of the investigator that C. difficile is the likely causative agent for the diarrhea.
3. Stool positive for C. difficile Toxin A and/or B antigen using an FDA or Health Canada approved/cleared EIA or ELISA laboratory test.
4. Participants with a primary episode or first recurrence of CDI are eligible.
5. In the judgment of the investigator, the expectation that the participant will survive with effective antibiotic therapy and appropriate supportive care for the anticipated duration of the study.
6. Female participants of childbearing potential must not be pregnant, plan to become pregnant during the study, or be breastfeeding; and must be willing to commit to either sexual abstinence or use highly effective methods of birth control contraception from screening through Day 70.
7. Males must use a condom and spermicide from screening through Day 70 (if the female partner(s) is of childbearing potential) and must not donate sperm from screening through Day 70.
8. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form.

Exclusion Criteria

1. Participants with any of the following conditions:

1. Intractable vomiting preventing oral medication intake
2. Severe underlying disease with an expected survival time less than the duration of the study (approximately 70 days).
3. More than 1 prior CDI occurrence within the last 3 months or more than 2 prior episodes of CDI in the last 12 months.
4. A history of a recent CDI episode within 3 months prior to enrollment that was non- responsive to vancomycin.
5. In the investigator's opinion, the participant is anticipated to require oral or intravenous systemic antibiotic therapy for a non-CDI infection between screening and Day 70.
6. Inflammatory bowel disease (Crohn's disease or ulcerative colitis), uncorrected Hirschsprung's disease, short gut syndrome, or any other condition known to significantly impact bowel motility and/or malabsorption.
7. Any other known pathogen associated with diarrhea.
8. Life-threatening or fulminant CDI as defined by IDSA/SHEA Guidelines.
9. Colonic perforation.
10. Need for concurrent laxatives or tube feeds, toxin binders, bile acid sequestrants during the study. Microbiota restoration therapy (MRT) or any phage therapy within 1 year of randomization. Receipt of bezlotoxumab within 3 months of randomization.
11. Participants treated with another antimicrobial agent directed at the current episode of CDI (metronidazole, fidaxomicin, rifaximin, tigecycline, or oral vancomycin) for \>24 hours of treatment within the 3 days prior to randomization will not be eligible for enrollment.
2. Pregnant or breastfeeding women.
3. Receipt of any investigational medication during the last month (30 days or 5 half lives, whichever is longer) prior to randomization.
4. Active and uncontrolled HIV with CD4 \<200/mm3.
5. Presence of active malignancy undergoing chemotherapy that is expected to cause significant immunosuppression, hematologic malignancy undergoing induction chemotherapy, or recent bone marrow or solid organ transplant (within 1 month prior to randomization) undergoing treatment with medications for the rejection of transplantation. In the investigator's opinion, is expected not to survive through the duration of the study (approximately 70 days) due to complications of the malignancy, or in the investigator's opinion will require oral or intravenous systemic antibiotic therapy during the study for malignancy related conditions.
6. Severe neutropenia defined as ANC \<500 cells/mm3
7. Severe hepatic impairment at screening including clinical signs of cirrhosis, end-stage hepatic disease (eg, ascites, hepatic encephalopathy), or Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3x upper limit of normal (ULN) or total bilirubin ≥ 2x ULN.
8. Any other surgical or medical condition (including a clinically significant laboratory abnormality) as determined by the investigator or the medical monitor, that could interfere with the participant's ability to participate in the study, the administration of study treatment, and/or the interpretation of study results that, in the investigator's opinion, may confound study assessments or study procedures.
9. Known hypersensitivity to CRS3123 or oral vancomycin.
10. An employee of the investigator or study center with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as a family member of the employee or the investigator.
11. Unwillingness to stop consuming non-dietary probiotics from randomization to Day 70.
12. Participants currently taking digoxin within 1 week of screening.
13. Unwillingness to refrain from consumption of grapefruit and its juices as well as nutraceutical supplements containing curcumin from randomization until 24 hours after EOT.
14. Unwillingness to stop use of anti-diarrheals from randomization to Day 70.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Crestone, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Urs Ochsner, PhD

Role: PRINCIPAL_INVESTIGATOR

Crestone, Inc

Locations

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131

Fullerton, California, United States

Site Status

117

Lancaster, California, United States

Site Status

143

Mission Hills, California, United States

Site Status

138

Orange, California, United States

Site Status

146

Miami, Florida, United States

Site Status

122

Miami, Florida, United States

Site Status

140

Marietta, Georgia, United States

Site Status

110

Idaho Falls, Idaho, United States

Site Status

129

Winfield, Illinois, United States

Site Status

130

Royal Oak, Michigan, United States

Site Status

139

Weldon Spring, Missouri, United States

Site Status

128

Butte, Montana, United States

Site Status

134

The Bronx, New York, United States

Site Status

147

Chapel Hill, North Carolina, United States

Site Status

114

Uniontown, Pennsylvania, United States

Site Status

104

Cedar Park, Texas, United States

Site Status

123

Houston, Texas, United States

Site Status

101

San Antonio, Texas, United States

Site Status

116

Calgary, Alberta, Canada

Site Status

120

London, Ontario, Canada

Site Status

Countries

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United States Canada

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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75N93019C00056

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

19-0021

Identifier Type: -

Identifier Source: org_study_id

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